Higashi K, Takasawa R, Yoshimori A, Goh T, Tanuma S, Kuchitsu K
Genome and Drug Research Center, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
Apoptosis. 2005 May;10(3):471-80. doi: 10.1007/s10495-005-1876-1.
Only few orthologs of animal apoptosis regulators have been found in plants. Recently, the ectopic expression of mammalian inhibitor of apoptosis proteins (IAPs) has been shown to affect plant programmed cell death. Here, we identified two novel proteins homologous to Arabidopsis thaliana IAP-like protein (AtILP) 1 and 2 by applying an improved motif searching method. Furthermore, homologs of AtILP1 were found to occur as a novel gene family in other organisms such as fungi and animals including Homo sapiens (HsILP1). Like baculovirus IAP repeats (BIRs) in IAPs, ILPs contain two highly conserved BIR-like domains (BLDs) with a putative C2HC-type zinc finger. Phylogenetic analyses indicated that ILPs are putative paralogs of IAPs. Homology modeling revealed that the three-dimensional structure of BLD in HsILP1 is similar to that of BIR. Transient expression of HsILP1 resulted in inhibition of etoposide-induced apoptosis in HEK293 and HeLaS3 cells. These findings suggest that ILPs are conserved in a wide range of eukaryotes including plants, and that their functions are closely related to those of IAPs.
在植物中仅发现了少数动物凋亡调节因子的直系同源物。最近，有研究表明哺乳动物凋亡抑制蛋白（IAPs）的异位表达会影响植物程序性细胞死亡。在此，我们通过应用一种改进的基序搜索方法，鉴定出了两种与拟南芥IAP样蛋白（AtILP）1和2同源的新蛋白。此外，在其他生物体如真菌和包括智人（HsILP1）在内的动物中，AtILP1的同源物以一个新的基因家族形式存在。与IAPs中的杆状病毒IAP重复序列（BIRs）一样，ILPs包含两个高度保守的类BIR结构域（BLDs）以及一个假定的C2HC型锌指。系统发育分析表明，ILPs是IAPs的假定旁系同源物。同源建模显示，HsILP1中BLD的三维结构与BIR相似。HsILP1的瞬时表达导致依托泊苷诱导的HEK293和HeLaS3细胞凋亡受到抑制。这些发现表明，ILPs在包括植物在内的广泛真核生物中是保守的，并且它们的功能与IAPs密切相关。
